11-cis-retinal and Diabetes-Mellitus--Type-2

Diabetic retinopathy is a common complication of type 2 diabetes and the leading cause of blindness in adults of working age. The aim of this work was to study the repercussions of high fat diet (HFD) induced diabetes on the retina of Meriones shawi (M.sh). Two groups of six M.sh each was studied. Group I was a normal control, fed with standard laboratory granules. In Group II, rodents received a HFD of enriched laboratory granules, for a period of 3 months. Body weight and plasma glucose were determined in the two groups. Retinal sections of the two groups were stained with the Hematoxylin-Eosin. Photoreceptors were identified by immunolabeling for rhodopsin (rods) and PNA (cones). Gliosis and microglial activation were identified by immunolabeling for GFAP and Iba-1. Labeling of calretinin and parvalbumin were also carried out to study the AII amacrine cells. Retinal layers thicknesses, gliosis, and specific neural cell populations were quantified by microscopy. The body weight (+77%) and plasma glucose (+108%) were significantly greater in the HFD rodents. Three months of HFD induced a significant loss of 38.77% of cone photoreceptors, as well as gliosis and an increase of 70.67% of microglial cells. Calcium homeostatic enzymes were depleted. This work shows that HFD in Meriones shawi induces a type II diabetes-like condition that causes loss of retinal neurons and photoreceptors, as well as gliosis. Meriones shawi could be a useful experimental animal model for this physiopathology particularly in the study of retinal neuro-glial alterations in Type II diabetes.

Topics: Amacrine Cells; Animals; Blood Glucose; Calbindin 2; Calcium; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Diet, High-Fat; Gene Expression; Gerbillinae; Glial Fibrillary Acidic Protein; Gliosis; Humans; Immunohistochemistry; Male; Microfilament Proteins; Microglia; Obesity; Parvalbumins; Retinal Cone Photoreceptor Cells; Retinal Rod Photoreceptor Cells; Rhodopsin

Previously it was shown that the circulating rhodopsin mRNA level was higher in diabetic retinopathy (DR). Recent evidence suggests that hypoxia may also be associated with DR. The aim of this study was to investigate the effect of oxygen desaturation on circulating retina-specific mRNA in type 2 diabetic patients. Thirty-five type 2 diabetic patients underwent overnight oximetry. Two parameters from oximetry were used to measure oxygen desaturation: the number of times per hour the oxygen saturation decreased by 4% or greater (number of dips/hr) and percentage of sleep time with oxygen saturation (SpO(2)) <90%. Blood samples were collected into PAXgene Blood RNA tubes. Total RNA was extracted from the samples and reverse-transcribed into cDNA, and retina-specific markers were measured by quantitative real time PCR. In patients with >/=5 dips/hr, mRNA values for rhodopsin (P= 0.05) and RPE65 (P= 0.044) were significantly higher than in patients with <5 dips/hr. No change was seen in retinoschisin mRNA expression. In patients with preproliferative or proliferative DR, median levels for rhodopsin mRNA and RPE65 mRNA were 30% and 80% higher and retinoschisin mRNA was lower in patients with >/=5 dips/hr when compared to patients with <5 dips/hr. These results indicate that hypoxia may modulate expression of genes in the retina.

Topics: Aged; Biomarkers; Carrier Proteins; cis-trans-Isomerases; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Eye Proteins; Female; Gene Expression Regulation; Humans; Hypoxia; Male; Middle Aged; Oximetry; Oxygen; Retina; Rhodopsin; RNA, Messenger

The experiments were designed to provide details on the characteristics of rhodopsin regeneration in the rod photoreceptors of diabetic mice and to evaluate their mechanistic basis.. A genetically-derived diabetic albino mouse was developed. An excised albino mouse eye preparation was used. The preparation allows for direct measurements of rhodopsin concentration and other spectrally distinct intermediates, and maintains the structural integrity of the compartments involved in rhodopsin regeneration. The experiments were conducted at moderate bleaching levels, averaging 13-14%, with mice that exhibited moderate levels of blood glucose concentration.. Rhodopsin regeneration was delayed in both genetically-derived and streptozotocin-injected diabetic mice when compared to non-diabetic mice. During the delay an intermediate of rhodopsin, N-Retinylidene Opsin (NRO440), that precedes the hydrolysis of the bleached chromophore from the opsin and that is associated with acidic conditions was observed. This intermediate was not observed in non-diabetic mice. The delay in rhodopsin regeneration of the diabetic mice was partially eliminated, and the relative concentration of NRO440 was decreased, when the internal pH of the rod photoreceptor was raised by modifying the perfusate composition.. Following a bleach, both genetic and streptozotocin diabetic mice exhibited abnormalities in rhodopsin regeneration. When studied at moderate bleaching levels with animals that were moderately diabetic, both groups of diabetic mice exhibited a delay in the start of the rhodopsin regeneration. The delay appears to be caused by the formation of an acid intermediate of the bleached rhodopsin resulting from acid conditions within the rod photoreceptors.

Topics: Acids; Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Hydrogen-Ion Concentration; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Photic Stimulation; Retinal Rod Photoreceptor Cells; Retinoids; Rhodopsin; Rod Opsins